Drug Trials Snapshots: AUSTEDO

HOW TO USE THIS SNAPSHOTThe information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the AUSTEDO Prescribing Information for complete information.

How is this drug used?

What are the benefits of this drug?

What are the benefits of this drug?

The table below summarizes the data on the primary efficacy endpoint. This was based on the Total Maximal Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28. The study compared the score at baseline to the average score at Weeks 9 and 12. The average score at Weeks 9 and 12 was called the “Maintenance Therapy” score or “Maintenance” score.

Table 2. Change from Baseline to Maintenance Therapy in Total Maximal Chorea (TMC)a Score in Patients Treated with AUSTEDO in Trial 1

Were there any differences in how well the drug worked in clinical trials among sex, and race groups?

The tables below summarize the responses to AUSTEDO by sex and age subgroups for the mITT population which includes all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the TMC score.

mITT: modified intent-to-treat; N: number of mITT patients; SD: standard deviation; TMC: total maximal chorea. a Obtained from all observations in the gender specific mITT population at maintenance, with the last available value method for missing data.

Adapted from FDA Statistical review

Table 4. Subgroup Analysis of Primary Endpoint by Age Group (mITT population)

Age

Change from Baseline to maintenance in TMC score

AUSTEDO

Placebo

< 65="">

N

38

35

Means (SD)a

-4.22 (2.84)

-2.17 (2.81)

≥ 65 years

N

7

10

Means (SD)a

-5.14 (3.64)

-1.35 (2.08)

mITT: modified intent-to-treat; N: number of mITT patients; SD: standard deviation; TMC: total maximal chorea.aObtained from all observations in the age group specific mITT population at maintenance, with the last available value method for missing data.

Adapted from FDA Statistical review

What are the possible side effects?

AUSTEDO may increase the risk of depression and suicide. Other serious side effects that AUSTEDO may cause include life threatening condition called neuroleptic malignant syndrome, restlessness (akathisia) and excessive sleepiness.

The most common side effects of AUSTEDO are sleepiness, diarrhea, dry mouth and tiredness.

What are the possible side effects?

The table below summarizes most common adverse reactions in the trial.

Table 5. Adverse Reactions in Trial 1 Experienced by at Least 4% of Patients on AUSTEDO and with a Greater Incidence than on Placebo

Adverse Reactions

AUSTEDO(N = 45)%

Placebo(N = 45)%

Somnolence

11

4

Diarrhea

9

0

Dry mouth

9

7

Fatigue

9

4

Urinary tract infection

7

2

Insomnia

7

4

Anxiety

4

2

Constipation

4

2

Contusion

4

2

AUSTEDO Prescribing Information

Were there any differences in side effects among sex, race and age?

Overall the number of patients in the trial was small, and the number of patients who experienced side effects in each subgroup was limited; therefore differences in side effect among sex, race and age subgroups could not be determined.

Were there any differences in side effects of the clinical trials among sex, and race groups?

The occurrence of side effects per demographic subgroup was low to allow for meaningful analysis.

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved AUSTEDO based primarily on evidence from one clinical trial that enrolled 90 patients with chorea associated with Huntington’s disease. The trial was conducted in 34 centers in the United States and Canada.

The figure below summarizes how many men and women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Adapted from FDA Statistical review

The figure and table below summarize the percentage of patients by race in the clinical trial.

Who participated in the trials?

The table below summarizes baseline demographics for the randomized population.

Table 6. Baseline Demographics for the Trial 1

Demographic Parameter

AUSTEDO(N=45)

Placebo(N=45)

Total(N=90)

Age (years)

Mean (SD)

55.4 (10.3)

52.1 (13.4)

53.7 (12.0)

Min, Max

23,74

30,73

23,74

Age Group (years), n (%)

< 65="">

38(84)

35 (78)

73 (81)

≥65 years

7 (16)

10 (22)

17(19)

Sex, n (%)

Men

22 (49)

28 (62)

50 (56)

Women

23 (51)

17 (38)

40 (44)

Race, n ( %)

White

45 (100)

38 (84)

83 (92)

Black or African American

0

5 (11)

5 (6)

Multiple

0

2 (4)

2 (2)

Ethnicity, n (%)

Non-Hispanic or Latino

45 (100)

45 (100)

45 (100)

Adapted from FDA Statistical review

How were the trials designed?

There was one trial that evaluated the benefit and side effects of AUSTEDO. In the trial, patients with chorea associated with Huntington’s disease were randomly assigned to receive either AUSTEDO or placebo for 12 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The trials measured overall change in chorea using Total Maximal Chorea Score. On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28.

How were the trials designed?

AUSTEDO was started at 6 mg per day and titrated upward, at weekly intervals, in 6 mg increments until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached.

The primary endpoint was the change from baseline to maintenance therapy in the Total Maximal Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.